Dr. Fu's central hypotheses relate to the pathogenesis of atherosclerosis. The PI has found evidence that monocytes which are known to penetrate the endothelium to become macrophages can differentiate within the neointima into foam cells. The latter, in part by their ability to synthesize and store lipids, are thought to play a key role in mediating critical steps in the progression to atherosclerosis. Using the procedure of subtractive hybridization, Dr. Fu has found a gene, ALBP that encodes a lipid binding protein, which may regulate the transformation of macrophages into foam cells. His specific aims are to pursue the functions of ALBP and to identify the transcription factors that initiate its expression; in particular, he focuses on the peroxisome-proliferator-activated receptor (PPAR). Importantly, his project also naturally extends to whether PPAR activated ALBP in response to artherogenic agents such as oxidized LDL or drugs used to treat insulin-resistant forms of diabetes.